A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto).

Abstract

518 Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC). Methods: GeparOcto (NCT02125344) patients (pts) received 18 weeks (wks) either EPC (3x E 150mg/m² q2w followed by 3x P225 mg/m² q2w followed by 3x C 2000mg/m² q2) or PM(Cb) (12x P 80mg/m² plus M 20 mg/m² q1w, plus Cb AUC 1.5 q1w in TNBC). For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included. Pts with HER2+ or TNBC were eligible irrespective of nodal status, luminal B-like tumours only if pN+. Primary objective compared pathologic complete response (pCR) rates (ypT0/is ypN0). Sample size calculations assumed a pCR rate of 50% for EPC and 60% for PM(Cb), requiring 950 pts to show superiority of PM(Cb). Secondary objectives compared pCR rates within the stratified subgroups (BC subtype, HER2+ vs HER2- HR+ vs HER2- HR-), amongst others. Results: 961 pts were recruited between 12/2014 and 05/2016, 945 started treatment. Median age was 48 years, 4% T3, 2% T4d, 46% N+, 82% ductal invasive, 66% G3 tumors; 40% were HER2+, 43% TNBC. 347 pts reported SAEs (176 EPC/171 PM(Cb)) and 2 pts died. 35 pneumonias (2 EPC vs 33 PM(Cb)) and 18 pneumonitis (3 EPC vs 15 PM(Cb)) were reported. 16.4% pts with EPC and 33.8% with PM(Cb) discontinued treatment (p<0.001), mainly due to AEs (47 EPC vs 113 PM(Cb)). Mean treatment duration was 17 wks with EPC and 16 wks with PM(Cb). pCR rate was 48.3% with EPC and 47.6% with PM(Cb)(OR 0.97 (95%CI 0.75-1.25), p=0.876). pCR rate in TNBC was 48.5% with EPC and 51.7% with PM(Cb); in HER2+ 62.0% vs 57.4% and in Luminal B 14.1% vs 14.6%. Conclusions: In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible. Clinical trial information: NCT02125344.